There is considerable interest in developing sensors that act as analogs of the mammalian olfactory system (Lundstrom et al. (1991) Nature 352:47-50; Shurmer and Gardner (1992) Sens. Act. B 8:1-11; Shurmer and Gardner (1993) Sens. Actuators B 15:32). In practice, most chemical sensors suffer from some interference by responding to chemical species that are structurally or chemically similar to the desired analyte. This interference is an inevitable consequence of the “lock” being able to fit a number of imperfect “keys”. Such interferences limit the utility, of such sensors to very specific situations.
Prior attempts to produce a broadly responsive sensor array have exploited heated metal oxide thin film resistors (Gardner et al. (1991) Sens. Act. B4:117-121; Gardner et al. (1991) Sens. Act. B 6:71-75), polymer sorption layers on the surfaces of acoustic wave resonators (Grate and Abraham (1991) Sens. Act. B 3:85-111; Grate et al. (1993) Anal. Chem. 65:1868-1881), arrays of electrochemical detectors (Stetter et al. (1986) Anal. Chem. 58:860-866; Stetter et al. (1990) Sens. Act. B 1:43-47; Stetter et al. (1993) Anal. Chem. Acta 284:1-11), conductive polymers or composites that consist of regions of conductors and regions of insulating organic materials (Pearce et al. (1993) Analyst 118:371-377; Shurmer et al. (1991) Sens. Act. B 4:29-33; Doleman et al. (1998) Anal. Chem. 70:2560-2654; Lonergan et al. Chem. Mater. 1996, 8:2298). Arrays of metal oxide thin film resistors, typically based on tin oxide (SnO2) films that have been coated with various catalysts, yield distinct, diagnostic responses for several vapors (Corcoran et al. (1993) Sens. Act. B 15:32-37). However, due to the lack of understanding of catalyst function, SnO2 arrays do not allow deliberate chemical control of the response of elements in the arrays nor reproducibility of response from array to array. Surface acoustic wave resonators are extremely sensitive to both mass and acoustic impedance changes of the coatings in array elements, but the signal transduction mechanism involves somewhat complicated electronics, requiring frequency measurement to 1 Hz while sustaining a 100 MHZ Rayleigh wave in the crystal. Attempts have also been made to construct arrays of sensors with conducting organic polymer elements that have been grown electrochemically through use of nominally identical polymer films and coatings. Moreover, Pearce et al., (1993) Analyst 118:371-377, and Gardner et al., (1994) Sensors and Actuators B 18-19:240-243 describe, polypyrrole based sensor arrays for monitoring beer flavor. Shurmer (1990) U.S. Pat. No. 4,907,441, describes general sensor arrays with particular electrical circuitry. U.S. Pat. No. 4,674,320 describes a single chemoresistive sensor having a semi-conductive material selected from the group consisting of phthalocyanine, halogenated phthalocyanine and sulfonated phthalocyanine, which was used to detect a gas contaminant. Other gas sensors have been described by Dogan et al., Synth. Met. 60, 27-30 (1993) and Kukla, et al. Films. Sens. Act. B., Chemical 37, 135-140 (1996).
Sensor arrays formed from a plurality of composites that consist of regions of a conductor and regions of an insulating organic material, usually an organic polymer as described in U.S. Pat. No. 5,571,401, have some advantages relative to the approaches described above, however there is a need for sensors and sensor materials that show dramatically improved detection sensitivity if the sensors and the sensing devices are to be as sensitive as the human olfactory system towards certain classes of compounds, such as amines or thiols. The composites composed of conductors and insulating organic material have sensitivities that are primarily dictated by the swelling-induced sorption of a vapor into the composite material, and analytes that sorb to similar extents produce similar swellings and therefore produce similar detected signals (Doleman, et al., (1998) Proc. Natl. Acad. Sci. U.S.A, 95, 5442-5447). However, the human nose shows greatly enhanced sensitivity towards biogenic amines and thiols than it does towards the corresponding chain-length alcohols or alkanes, whereas this property is not displayed by composites that consist of regions of conductor and regions of a swellable insulator, whose swelling is similar for amines, thiols, alkanes, alcohols, and other materials of similar vapor pressure to each other. Certain odors have typically been missed by an electronic nose that is not responsive to such odors at least at the level comparable to a human, and such a device will not be acceptable to detect and classify odors that are perceived by humans or at levels that are desirable for food freshness, biomedical, disease state identification, and other applications.
Breath testing has long been recognized as a nonintrusive medical technique that allows for diagnosis of disease or the presence of analytes. Presently, the techniques utilized for the evaluation of breath are gas chromatography with flame photometric detection (FPD), GC/MS (mass spectrometry), the Halimeter, microbiological testing, and organoleptic scores (Spielman, 1998). Both GC/FPD and GC/MS are quantitative techniques, with GC/MS having the added advantage of identifying the individual components of analyzed breath. However, both of these instruments are costly and time intensive, which limits their use in common practice. The Halimeter is a portable, electrochemically-based sulfide monitor introduced within the last decade to monitor for halitosis by measuring the concentration of sulfur containing compounds semiquantitatively at the part per billion level. However, one drawback is that the Halimeter is unable to detect individual sulfur compounds, because it is comprised of a single sensor that responds to the general class of sulfur containing compounds, such as hydrogen sulfide and methylmercaptan. Furthermore, it is unable to detect many other objectionable odoriferous compounds such as indole, skatole, volatile fatty acids, and amines, which are present in breath of halitosis patients. Additionally, the halimeter sensor is not entirely selective because it also responds to alcohols such as ethanol. In addition, it can not detect the presence of volatile amines or other compounds that are of interest in disease other than certain types of halitosis. Odor panels have been utilized efficiently in some cases for the analysis of disease. Some of the drawbacks are of course that odor panels consist of humans that are genetically capable and highly trained, and that the scores are subjective.
Although the foregoing systems have some usefulness, there still remains a need in the art for a low cost, broadly responsive analyte detection sensor array based on a variety of sensors.